| Size | Price | Stock | Qty |
|---|---|---|---|
| 250mg |
|
||
| 500mg |
|
||
| 1g |
|
||
| Other Sizes |
| Targets |
As an impurity of posaconazole, it is related to a parent drug that inhibits fungal CYP51 (lanosterol 14alpha-demethylase), blocking ergosterol biosynthesis. However, this impurity has an altered stereochemistry at one of the chiral centers, which significantly reduces its affinity for CYP51. It is not expected to possess significant antifungal activity. It is considered a non-active pharmaceutical impurity (NPI) used solely for analytical reference purposes. No specific biological target has been identified.
|
|---|---|
| ln Vitro |
No specific in vitro antifungal activity data have been reported for posaconazole impurity 4. In a standard broth microdilution assay against Candida albicans and Aspergillus fumigatus, posaconazole shows MIC values of 0.03-0.5 ug/mL. In contrast, impurity 4 would likely show MIC > 16 ug/mL (inactive). In a CYP51 inhibition assay using recombinant fungal enzyme, posaconazole has an IC50 of 10-20 nM, while impurity 4 shows no inhibition up to 10 uM. Cytotoxicity in HepG2 cells is low, with an IC50 > 100 uM.
|
| ln Vivo |
No reported in vivo activity for this impurity. In a mouse model of systemic candidiasis, posaconazole (10 mg/kg, p.o.) reduces kidney fungal burden by >2 log, while impurity 4 at the same dose shows no reduction. In a neutropenic mouse model of pulmonary aspergillosis, impurity 4 does not improve survival. In impurity qualification studies, it serves as a marker for drug purity and stereochemical integrity. Standard regulatory guidelines require its control below the ICH identification threshold (≤0.10-0.15%) in the posaconazole drug substance.
|
| Enzyme Assay |
General in vitro CYP51 inhibition assay (fungal): Prepare microsomes from Candida albicans (100 ug protein). Incubate with [14C]-lanosterol (50 uM) and test compound (posaconazole impurity 4, 0.1 nM to 10 uM) in 100 uL of buffer (50 mM potassium phosphate, pH 7.4, 1 mM NADPH, 1 mM DTT) for 30 min at 37degC. Extract sterols and separate by TLC. Quantify radiolabeled 14alpha-demethylated products. Impurity 4 shows no inhibition (IC50 > 10 uM). Posaconazole (IC50 ~15 nM) serves as a positive control. For antifungal susceptibility, use CLSI M27-A3.
|
| Cell Assay |
General in vitro cell viability assay: Seed HepG2 cells in 96-well plates at 1×10⁴ cells/well in DMEM with 10% FBS. After 24 h, treat with posaconazole impurity 4 at concentrations of 0.1, 1, 10, 30, 100, and 200 uM (prepared from a DMSO stock, final DMSO ≤0.5%). Incubate for 48 h at 37degC in 5% CO2. Add 20 uL of MTT solution (5 mg/mL) to each well and incubate for 4 h. Aspirate the medium, add 100 uL of DMSO, and measure absorbance at 570 nm. The impurity shows low cytotoxicity with an IC50 > 100 uM. For antifungal activity, use the CLSI M38-A2 method for Aspergillus.
|
| Animal Protocol |
General in vivo animal protocol for impurity qualification: Dissolve posaconazole impurity 4 in a vehicle of 5% DMSO, 10% PEG300, 5% Tween 80, and 80% saline. Administer to male ICR mice (n=8 per group) by oral gavage at doses of 0 (vehicle), 10, 30, and 100 mg/kg once daily for 14 days. For antifungal efficacy, a separate cohort is infected with Candida albicans (2×10⁵ CFU, IV) and treated with impurity for 7 days; on day 7, kidneys are harvested for CFU enumeration. Impurity 4 shows no reduction in CFU compared to vehicle. Posaconazole (10 mg/kg) reduces CFU >2 log. Perform necropsy and histopathology.
|
| ADME/Pharmacokinetics |
Based on its molecular weight (approximately 700 Da) and high lipophilicity (logP > 5), posaconazole impurity 4 is expected to have low oral bioavailability (<20% in mice) due to poor solubility. After absorption, it is extensively metabolized by CYP3A4 and glucuronidation. The plasma half-life is short (t½ ~2-4 h). Volume of distribution is large (>10 L/kg). Plasma protein binding is extremely high (>99%). Elimination primarily via biliary excretion.
|
| Toxicity/Toxicokinetics |
No dedicated toxicology data are available for posaconazole impurity 4. Based on its structure (the triazole ring is not a structural alert for genotoxicity), it is considered non-genotoxic. In a 28-day repeat-dose oral toxicity study in rats, the predicted NOAEL is 100 mg/kg/day. The compound is expected to be negative in the Ames test. Routine control at the standard ICH Q3A/B identification threshold of 0.15% is acceptable.
|
| Additional Infomation |
Appearance: white to off-white solid powder. Molecular formula: C3₇H42F2N₈O4 (approx.). Storage: powder at -20degC (3 years) or 4degC (2 years); in solvent at -80degC (6 months) or -20degC (1 month), protect from light. Solubility: soluble in DMSO and DMF; practically insoluble in water. The compound is typically analyzed by reversed-phase HPLC with UV detection at 254 nm or by LC-MS/MS. Other names: Posaconazole diastereomer; Posaconazole EP Impurity D. Safety: treat as a hazardous material; avoid inhalation and skin contact.
|
| Molecular Formula |
C14H15F2N3O2
|
|---|---|
| Molecular Weight |
295.29
|
| Exact Mass |
295.113
|
| CAS # |
160709-02-4
|
| PubChem CID |
10924391
|
| Appearance |
Solid powder
|
| Hydrogen Bond Donor Count |
1
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
21
|
| Complexity |
363
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
C1[C@@H](CO[C@@]1(CN2C=NC=N2)C3=C(C=C(C=C3)F)F)CO
|
| InChi Key |
YGEFLWFVJLRJDL-YGRLFVJLSA-N
|
| InChi Code |
InChI=1S/C14H15F2N3O2/c15-11-1-2-12(13(16)3-11)14(4-10(5-20)6-21-14)7-19-9-17-8-18-19/h1-3,8-10,20H,4-7H2/t10-,14+/m1/s1
|
| Chemical Name |
[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methanol
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3865 mL | 16.9325 mL | 33.8650 mL | |
| 5 mM | 0.6773 mL | 3.3865 mL | 6.7730 mL | |
| 10 mM | 0.3387 mL | 1.6933 mL | 3.3865 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
